σ N–C Bond Difunctionalization in Bridged Twisted Amides: Sew-and-Cut Activation Approach to Functionalized Isoquinolines

A rare example of
highly selective σ N–C bond difunctionalization
in bridged twisted lactams through N–C cleavage has been achieved.
In combination with the intramolecular Heck cyclization, this method
affords a two-step bond reorganization event (“sew-and-cut”)
to access functionalized isoquinoline ring systems directly with high
atom economy. C–H bond functionalizations directed by a weakly
coordinating bridged amide bond increase scaffold diversity. Preliminary
mechanistic studies on the effect of amide distortion and the role
of electrophile in this unusual σ N–C amide difunctionalization
are described.